DESCRIPTION (provided by candidate): The nucleus accumbens (NAc) is a brain area integral to the development and expression of addiction-related behaviors. Neurons in the NAc show drug-induced changes in morphology, synaptic and intrinsic physiology, and gene expression. In both human and animal studies, females show greater susceptibility to drug addiction than males. It is unknown to what extent the sex differences in behavioral responses to drugs of abuse are accompanied by differences in the synaptic or intrinsic physiology of NAc neurons. Recent evidence from a number of laboratories suggests that many of the physiological changes in the NAc in response to repeated drug treatment are .modulated or intensified by a period of abstinence. This suggests that chronic drug exposure may serve to prime the brain for rewiring that takes place during the abstinence period. The proposed experiments will address three main questions: 1) Are there underlying sex differences in the synaptic and intrinsic physiology of NAc neurons? 2) Are the morphological changes seen after chronic cocaine and subsequent abstinence reflected by physiological changes in the NAc, and does the physiological response differ between males and females? 3) What is the role of the abstinence period in producing these changes, and do males and females differ in the effect of abstinence? Using whole-cell patch clamp electrophysiology in acute slices of the NAc from male and female rats, I will ask whether chronic treatment with saline or cocaine affects the synaptic and intrinsic physiology of NAc neurons in males and females after 30 days of abstinence, a time at which robust morphological changes are observed in response to chronic cocaine. I will also evaluate the effects of chronic saline or cocaine on NAc physiology without an extended abstinence period in males and females. These studies will provide insight about how chronic drug exposure produces lasting changes in brain physiology. My results will also help us understand the physiological underpinnings of behavioral sex differences in addiction as well as the role of the abstinence period, which could help to provide individually-targeted treatment approaches based on addicts'gender and drug history.